Do polygenic risk and stressful life events predict pharmacological treatment response in obsessive compulsive disorder? A gene-environment interaction approach

被引:18
作者
Alemany-Navarro, Maria [1 ,2 ]
Costas, Javier [3 ]
Real, Eva [1 ,2 ]
Segalas, Cinto [1 ,2 ]
Bertolin, Sara [2 ]
Domenech, Laura [4 ,5 ,6 ]
Rabionet, Raquel [4 ,5 ,6 ]
Carracedo, Angel [3 ,7 ,8 ]
Menchon, Jose M. [1 ,2 ,9 ,10 ]
Alonso, Pino [1 ,2 ,9 ,10 ]
机构
[1] Inst Invest Biomed Bellvitge IDIBELL, Lhospitalet De Llobregat, Barcelona, Spain
[2] Hosp Univ Bellvitge, Dept Psychiat, OCD Clin & Res Unit, Lhospitalet De Llobregat, Barcelona, Spain
[3] Inst Invest Sanitaria Santiago, Grp Xenet Psiquiatr, Serv Galego Saude, Complexo Hosp Univ Santiago de Compostela, Santiago De Compostela, Spain
[4] Barcelona Inst Sci & Technol, Ctr Genom Regulat CRG, Dr Aiguader 88, Barcelona 08003, Spain
[5] Univ Pompeu Fabra, Barcelona, Spain
[6] CIBER Epidemiol & Publ Hlth CIBERESP, Barcelona, Spain
[7] Univ Santiago Compostela, Ctr Nacl Genotipado, Inst Carlos III, Grp Med Xenom, Santiago De Compostela, Spain
[8] Ctr Invest Biomed Red Enfermedades Raras, Santiago De Compostela, Spain
[9] Inst Salud Carlos III, CIBERSAM Ctr Invest Red Salud Mental, Madrid, Spain
[10] Univ Barcelona, Dept Clin Sci, Bellvitge Campus, Barcelona, Spain
关键词
GENOME-WIDE ASSOCIATION; SEROTONIN REUPTAKE INHIBITORS; CHILDHOOD MALTREATMENT; PARTITIONING HERITABILITY; ANTIDEPRESSANT TREATMENT; CLINICAL PREDICTORS; VARIANTS; TRAUMA; POLYMORPHISMS; METAANALYSIS;
D O I
10.1038/s41398-019-0410-0
中图分类号
R749 [精神病学];
学科分类号
100205 ;
摘要
The rate of response to pharmacological treatment in Obsessive-compulsive disorder (OCD) oscillates between 40 and 70%. Genetic and environmental factors have been associated with treatment response in OCD. This study analyzes the predictive ability of a polygenic risk score (PRS) built from OCD-risk variants, for treatment response in OCD, and the modulation role of stressful life events (SLEs) at the onset of the disorder. PRSs were calculated for a sample of 103 patients. Yale-Brown Obsessive Compulsive Scale (YBOCS) scores were obtained before and after a 12-week treatment. Regression analyses were performed to analyze the influence of the PRS and SLEs at onset on treatment response. PRS did not predict treatment response. The best predictive model for post-treatment YBOCS (post YBOCS) included basal YBOCS and age. PRS appeared as a predictor for basal and post YBOCS. SLEs at onset were not a predictor for treatment response when included in the regression model. No evidence for PRS predictive ability for treatment response was found. The best predictor for treatment response was age, agreeing with previous literature specific for SRI treatment. Suggestions are made on the possible role of neuroplasticity as a mediator on this association. PRS significantly predicted OCD severity independent on pharmacological treatment. SLE at onset modulation role was not evidenced. Further research is needed to elucidate the genetic and environmental bases of treatment response in OCD.
引用
收藏
页数:10
相关论文
共 83 条
  • [11] Exon-focused genome-wide association study of obsessive-compulsive disorder and shared polygenic risk with schizophrenia
    Costas, J.
    Carrera, N.
    Alonso, P.
    Gurriaran, X.
    Segalas, C.
    Real, E.
    Lopez-Sola, C.
    Mas, S.
    Gasso, P.
    Domenech, L.
    Morell, M.
    Quintela, I.
    Lazaro, L.
    Menchon, J. M.
    Estivill, X.
    Carracedo, A.
    [J]. TRANSLATIONAL PSYCHIATRY, 2016, 6 : e768 - e768
  • [12] An investigation of traumatic life events and obsessive-compulsive disorder
    Cromer, Kiara R.
    Schmidt, Norman B.
    Murphy, Dennis L.
    [J]. BEHAVIOUR RESEARCH AND THERAPY, 2007, 45 (07) : 1683 - 1691
  • [13] Genetic Studies on the Tripartite Glutamate Synapse in the Pathophysiology and Therapeutics of Mood Disorders
    de Sousa, Rafael T.
    Loch, Alexandre A.
    Carvalho, Andre F.
    Brunoni, Andre R.
    Haddad, Marie Reine
    Henter, Ioline D.
    Zarate, Carlos A., Jr.
    Machado-Vieira, Rodrigo
    [J]. NEUROPSYCHOPHARMACOLOGY, 2017, 42 (04) : 787 - 800
  • [14] Association testing of the positional and functional candidate gene SLC1A1/EAAC1 in early-onset obsessive-compulsive disorder
    Dickel, Diane E.
    Veenstra-VanderWeele, Jeremy
    Cox, Nancy J.
    Wu, Xiaolin
    Fischer, Daniel J.
    Van Etten-Lee, Michelle
    Himle, Joseph A.
    Leventhal, Bennett L.
    Cook, Edwin H.
    Hanna, Gregory L.
    [J]. ARCHIVES OF GENERAL PSYCHIATRY, 2006, 63 (07) : 778 - 785
  • [15] DOLD M, 2015, EUR PSYCHIAT, V30
  • [16] The effect of childhood trauma on pharmacological treatment response in depressed inpatients
    Douglas, Katie M.
    Porter, Richard J.
    [J]. PSYCHIATRY RESEARCH, 2012, 200 (2-3) : 1058 - 1061
  • [17] Power and Predictive Accuracy of Polygenic Risk Scores
    Dudbridge, Frank
    [J]. PLOS GENETICS, 2013, 9 (03):
  • [18] Interneuron Simplification and Loss of Structural Plasticity As Markers of Aging-Related Functional Decline
    Eavri, Ronen
    Shepherd, Jason
    Welsh, Christina A.
    Flanders, Genevieve H.
    Bear, Mark F.
    Nedivi, Elly
    [J]. JOURNAL OF NEUROSCIENCE, 2018, 38 (39) : 8421 - 8432
  • [19] Association analysis of SLC6A4 and HTR2A genes with obsessive-compulsive disorder: Influence of the STin2 polymorphism
    Ferreira Gomes, Chayenne Karine
    Vieira-Fonseca, Tamiris
    Melo-Felippe, Fernanda Brito
    de Salles Andrade, Juliana Braga
    Fontenelle, Leonardo F.
    Kohlrausch, Fabiana Barzotti
    [J]. COMPREHENSIVE PSYCHIATRY, 2018, 82 : 1 - 6
  • [20] Evidence-based pharmacotherapy of obsessive-compulsive disorder
    Fineberg, NA
    Gale, TM
    [J]. INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY, 2005, 8 (01) : 107 - 129